This project will continue work already in progress to demonstrate the manner in which respiratory mechanics (lung compliance, resistance, work of breathing) interact with blood chemistry (PO2, PCO2, pH) in the overall regulation of respiration. Work to date shows that reflexes primarily responsive to lung mechanics are responsive earlier in conditions such as congestive heart failure and pulmonary embolism than are the chemoreflexes. The mechanical reflexes were shown to increase breathing rate and only when they failed to maintain stable mechanical conditions were there changes in blood chemistry to cause increased ventilation. Continuing this work, the chemoreflex system was stressed by varying CO2 and O2 content of the inspired air, while the mechanoreflex system was stressed by applying negative pressure with a body plethysmograph. This work showed that the sensitivity of chemical reflexes was influenced by changes in lung mechanics and also that the mechanoreflex system was affected by changes in inspired gas content. The proposed project will use data already accumulated to devise a mathematical model for the control of respiration which defines the interaction of both the chemical and mechanical reflex systems. Following development of the model, clinical application of the principles developed will be devised for assisting in the management of respiratory distress conditions such as are seen in congestive heart failure, emphysema, asthma, and in acute respiratory insufficiency.